effects of low-dose maintenance peg interferon alfa-2b therapy versus supportive care in patients with cirrhotic hepatitis c with hiv (study p04371)

Conditions: Hepatitis C; Liver Cirrhosis; HIV Infections

Summary: this is a phase 3b, randomized, open-label, parallel-group, multi-center, multi-national study of low-dose maintenance peg interferon alpha-2b (peg-intron®) in subjects with human immunodeficiency virus-hepatitis c virus (hiv-hcv) co-infection. the primary objective is to compare at end of study the efficacy of peg-intron® monotherapy (0.5 µg/kg subcutaneously once weekly for 24-36 months) versus standard supportive care, using the time to any of the following clinical events (death, decompensation, liver transplant, hepatocellular carcinoma \[hcc\]) as endpoints.


Eligibility criteria:
inclusion criteria: * age at least 18 years but \< 70 years, of either sex or any race. * detectable plasma hepatitis c virus (hcv) rna (all genotypes of hcv are permitted). * cirrhosis of the liver within the last five years. * compensated liver disease (child-pugh \<8 with hepatic encephalopathy \<= 1. * no evidence of hepatocellular carcinoma (hcc) and a serum alpha fetoprotein (afp) \<100 ng/ml within two months of randomization/study enrollment. * varices results via endoscopy within the last six months or at time of screening. * serologic evidence of human immunodeficiency virus-1. * cd4 cell count \>=100 /µl. * platelet number of at least 50000 mm\*\*3. * neutrophil count of at least 750 mm\*\*3. * hemoglobin of \>9.0 mg%. * serum thyroid stimulating hormone levels within normal limits, regardless of treatment with l thyroxin. * hemoglobin a1c (hba1c)\<8.5%, to demonstrate controlled diabetes, if applicable. * written clearance from an ophthalmologist must be presented for subjects with a history of hypertension or diabetes prior to treatment start. * creatinine clearance \>50 ml/min, as assessed by the indirect calculation method. * demonstrate stable status of hiv-1 infection. * on stable antiretroviral therapy (haart) for at least 6 weeks prior to baseline, with the expectation of their haart regimen (drugs and dosage) remaining unaltered for the first 8 weeks of the study or * willing to delay initiation of haart therapy for at least 6 weeks (for subjects who have not been on haart for at least 8 weeks prior to randomization). "structured treatment interruptions" will be permitted during the study. * counseled in the appropriate use of birth control while in this study, as confirmed by the principal investigator or a sub-investigator. * free of any clinically significant disease (other than hcv and hiv) that would interfere with study evaluations. exclusion criteria: * female who is pregnant, intends to become pregnant during the study or within two months after study completion, or is nursing. male subject whose partner wants to become pregnant. * using silymarin. * positive test at screening for anti-hav igm ab, hbsag, anti-hbc igm ab, or hbeag. * any cause of liver disease other than chronic hepatitis c. * suspected or having hypersensitivity to interferon. * history of liver decompensation status or other evidence of bleeding from esophageal varices, signs of current bleeding, significant ascites, hepatic encephalopathy, jaundice or other conditions consistent with decompensated liver disease. * present with a lesion suspicious for hepatic malignancy on the screening imaging. * any active malignant disease, suspicion, or history of malignant disease within 5 years prior to study enrollment (except for adequately treated basal cell carcinoma). * known coagulation or hemoglobin diseases. * organ transplant, except corneal or hair transplant. * any known preexisting medical condition that, in the investigator's opinion, could interfere with the subject's participation in and completion of the study, such as major depressive disorder. * active hiv-related opportunistic infection and/or malignancy requiring systemic therapy. * evidence of known severe retinopathy. * subject has not observed the designated washout periods for any of the prohibited medications. * participating in any other hepatitis c clinical study.